Ongoing studies are designed to test the hypothesis that hypertension of thoracic aortic coarctation, as a model of "total renal underperfusion", is renin-mediated. The postulated pathogenetic sequence includes initial hyperfusion of total renal mass greater then increased renin activity greater then increased blood pressure and aldosterone; subsequently, compensatory renin/aldosterone-induced volume expansion acts to sustain hypertension while permitting normalization of renal perfusion and renin activity. While indices of either renin or volumes may be "normal" depending on sodium intake, the renin:volume relationship should be consistently abnormal. In inbred dogs with neonatally-indced thoracic coarctation and in littermate controls, we are currently examining blood pressure with indies of renin, body fluid volumes, and renal perfusion during developing and establishing phases of coarctation hypertension. Spontaneous changes with time and responses to dietary salt manipulation are being assessed for the following: 1) Indirect forelimb and hindlimb blood pressure; 2)24Na space; 3) radioiodinated serum albumin space; 4) plasma renin activity, renin concentration and renin substrate concentration, all by radioimmunoassay of angiotensin I; 5) renal clearance of insulin and para aminohippurate; and 6) blood pressure (including direct at one year post-banding) response to angiotensin blockade by converting-enzyme inhibitor. Studies are also designed to clarify the physiologic significance of the in vitro acceleration of the renin reaction, measured as increased renin reactivity and observed in several hypertensive states including coarctation hypertension. Finally, since the renal pressor system and renal mass are intact in the neonatal coarctation model, results will provide information on the basic physiology of renin-angiotension-volume homeostasis in the unanesthetized dog. Confirmation of the hypothesis will mandate revision of current criteria for diagnosing renin-mediated mechanisms in hypertensive patients.